The invention relates generally to magnetic resonance imaging (MRI) and analytical magnetic resonance spectroscopy (MRS), more particularly to calibration of MRI and MRS scanners when employing labeled contrast agents such as 13C based contrast agents.
Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) are diagnostic techniques that are particularly attractive to physicians in that the techniques do not involve exposing a patient under study to potentially harmful radiation, such as X-rays. Further, both techniques have advantages over other available imaging platforms when analyzing metabolic characteristics and regions of interest in a patient. Analytical high resolution nuclear MRS is routinely used in the determination of molecular structure.
Until recently, MRI and MRS have lacked sensitivity due to the normally very low polarization of the nuclear spins of the samples used. A number of techniques exist to improve the polarization of nuclear spins in the solid phase. These techniques are known as hyperpolarization techniques and lead to an increase in sensitivity. As used herein, the term “hyperpolarize” or “hyperpolarization” refers to changing the distribution of spins on the available spin states from the Boltzmann distribution. The resulting hyperpolarization is higher than the polarization given by the Boltzmann distribution, which is a function of temperature and magnetic field strength. These concepts and methods for hyperpolarization are further described in U.S. Pat. No. 6,466,814.
In hyperpolarization techniques, a sample of a labeled imaging agent, for example 13C Pyruvate or another similar polarized metabolic imaging agent, is introduced or injected into the subject being imaged.
Given the ubiquitous presence of carbon atoms in most metabolic processes, and the large chemical shift of the 13C nuclei, 13C spectroscopy is very promising for following metabolism in vivo. Given the low gyromagnetic ratio of the 13C nuclei, however, even images/spectra aided by the infusion of labeled compounds suffer from low resolution or low signal to noise, making their utility in a clinical setting somewhat questionable.
The recent development of hyperpolarization techniques can dramatically change the impact that 13C MRI and MRS can have in managing a variety of pathological conditions. Real time imaging of metabolism has been reported in a variety of animal models of disease using MRI of 13C labeled, hyperpolarized compounds. In order to successfully translate the results of research performed in animals to humans, care must be taken when imaging such compounds, to insure that the maximum information is extracted using the minimum relevant agent dose. The hyperpolarized signals are large, non-renewable and fast decaying, and require special attention when imaged, to extract the maximum image signal to noise (SNR) per injected agent dose.
Many pulse sequences require precise flip angle calibration to produce high SNR, artifact-free images. Moreover, quantification of compound concentration relies on precise knowledge of the excitation flip angle. For most MRI or MRS scans, flip angle calibration is performed in a prescan step, at the same frequency as the one used for imaging. For infusion or injection of 13C labeled (or labeled and hyperpolarized) compounds, such calibration step is challenged by the low availability of natural abundance signal prior to injection (at least in certain anatomical areas, such as the brain), and by the variable nature of the signal following injection. One approach to overcome these difficulties is to use a phantom loading the coil in a manner similar to the way a patient would load it, and perform a flip angle calibration on that phantom prior to any patient scan. The same transmit gain setting would then be used for all the in vivo studies.
However, in 23Na scans of human brains, for example, the transmit power can vary by as much as 2 dB from subject to subject. It is clear, therefore, that a common calibration to be used for all subjects would be imprecise, and could lead to image signal loss for pulse sequences that are sensitive to flip angle calibration (such as spin echoes), or to error in quantifying metabolite concentrations.
What is needed is a system and method and system for imaging using labeled contrast agents, such as metabolic imaging agents, that overcome the problems and challenges described above.